If Trump, who is riding a wave of anti-establishment anger, manages to snatch a surprise victory in the Midwestern US state, it could suffocate the campaign of his main rival Ted Cruz.
"If we do well here, folks, it's over," Trump claimed at a campaign stop Monday in the town of La Crosse.
Like Trump, Democratic frontrunner Hillary Clinton risks losing Wisconsin, as she faces a surging Bernie Sanders who has won five of the last six contests.
April could ultimately prove a sunny month for Clinton, as the former secretary of state leads Sanders by double digits in New York, which votes April 19, and Pennsylvania which casts ballots a week later.
Trump, the 69-year-old real estate mogul from New York, leads handily in those states also.
Wisconsin, the birthplace of the Republican Party, is seen as Ground Zero for the anti-Trump movement as the race enters a pivotal phase.
Should they halt Trump there, it would bolster the presidential campaign of Cruz, the 45-year-old conservative senator from Texas.
For Cruz, whose campaign is seen as the last chance to prevent a Trump nomination, "it's a very important win. For Trump, it's not a critical loss," University of Iowa professor Timothy Hagle told AFP.
It has been a bumpy period for Trump. Though his campaign has seemed bulletproof up until now, his latest controversial statements — on abortion, Cruz's wife and a journalist who said she was roughed up by Trump's campaign manager — have further alienated women voters, polls indicate.
With Wisconsin polls showing Cruz leading, Trump barnstormed the heartland state.
And perhaps as a way to soothe women voters' concerns about Trump and soften his image, his wife Melania was set to join him Monday on the campaign trail.
- Turning point? -
Trump doubled down on some of his controversial recent assertions — that the United States should consider leaving NATO, and that Japan should be responsible for its own nuclear defense.
"I want to help other nations. But we don't want to be the fools, we don't want to be the dumb patsies that we are all over the world," he said Monday, slamming NATO members that "haven't been paying" their share for years.
The winner of Tuesday's Republican primary will take most of the 42 delegates on offer. If Cruz wins, he will claim it as a turning point in the race, but mathematically speaking he will struggle to overcome his delegate deficit.
Currently, Trump has 739 delegates, Cruz has 466 and Ohio Governor John Kasich has 145, according to a CNN tally. A candidate needs 1,237 delegates to win the Republican nomination outright.
On Monday, Trump called for Kasich to "get the hell out" of the race. But Kasich has refused, insisting he would be the logical mainstream choice in the event of a contested convention in July.
Trump stressed he could sew up the nomination before the confab in Cleveland.
"I think we're going to get there on the 1,237 if you want to know the truth," Trump predicted.
Cruz was similarly positive, telling Wisconsin voters that "our campaign still has a clear path" to crossing the delegate threshold before the convention.
Some experts swatted back the assertion.
"There's no chance he can get to 1,237," veteran election watcher Larry Sabato of the University of Virginia said of Cruz.
"It's simply a matter of whether Trump gets to 1,237. If he does, it's over," Sabato added.
"If he doesn't, then we go on to other ballots (at the convention) and anything can happen."
Clinton meanwhile spent Sunday and Monday morning in New York, returning only Monday night to Wisconsin, a possible sign of how she sees her chances there.
"Between you and me, I don't want to get Hillary Clinton more nervous than she already is. She's already under a lot of pressure," Sanders quipped to voters in Janesville.
"So don't tell her this, but I think we win here, we win in New York state, we're on our way to the White House."
Grass-roots enthusiasm for the self-proclaimed democratic socialist remains high. He outraised the Clinton juggernaut in March, pulling in a stunning $44 million in donations against $29.5 million for Clinton.
But in order to prevail in the all-important delegates race, Sanders would need to win at least 60 percent of remaining delegates.